Comparison of verapamil and bepridil, two slow channel inhibitors, in protection against calcium-induced arrhythmias.

Verapamil and bepridil share the common property of antagonizing the slow inward calcium-mediated current, but bepridil has some additional antiarrhythmic properties. The efficacy of these two compounds against CaCl2-induced arrhythmias has been compared in rats. CaCl2 was administered i.v. by continuous infusion until death (25 mg X kg-1 X min-1 or 40 mg X kg-1 X min-1) or by bolus injection (160 mg X kg-1). Bepridil (5, 10 mg X kg-1) or verapamil (2.5, 5 mg X kg-1) were injected 10 min before CaCl2. Bepridil (10 mg X kg-1) or verapamil (5 mg X kg-1) prolong the survival time during CaCl2 infusion. After pretreatment, the injection of 160 mg X kg-1 CaCl2 is less toxic: 25% of animals are protected by bepridil (5 mg X kg-1), 41% by bepridil (10 mg X kg-1) or verapamil (5 mg X kg-1). At death the myocardial Ca2+ level is not different in controls and pretreated animals, thus, the ratio myocardial Ca2+/total injected Ca2+ is significantly lowered by bepridil (10 mg X kg-1) or verapamil (5 mg X kg-1). The efficacy of the two drugs on this model appears related solely to inhibition of slow inward current despite the additional antiarrhythmic profile of bepridil.